Expression of cell-cycle regulators, cyclin E and p21(WAF1/CIP1) potentialprognostic markers for gastric cancer

Aims: The deregulation of cyclin, cyclin-dependent kinases (CDKs) and their inhibitors could have a crucial role in the development of diverse human c ancers. Methods: In this study, we analysed the expression of cyclin D1, cyclin E, p21(WAF1/CIP1) and p27(KIP1) in 84 surgically resected gastric cancers by i mmunohistochemistry with long-term follow-up (median 38 months). We also ev aluated the relation between each cell cycle regulator and various clinicop athological findings, including age, sex, histological grade, tumour locati on, tumour type and stage and lymph-node metastasis. Results: Overexpression of cyclin D1 and E was detected in 21/84 (25%) and 34/84 (40.5%) patients, respectively. Normal gastric epithelium showed cons istently positive immunostain for p21(WAF1/CIP1) and p27(KIP1) in more than 50% of nuclei. Loss of p21(WAF1/CIP1) and p27(KIP1) expression was noted i n 45/84 (53.6%) and 44/54 (52.4%) patients, respectively. Among the various clinicopathological findings, overexpression of cyclin E was associated wi th lymphnode metastasis (P=0.003) and recurrence (P=0.043). Loss of p21(WAF 1/CIP1) expression was more frequent in diffuse type cancers (P=0.005) and was correlated with recurrence (P=0.002) and death (P=0.002). Overexpressio n of cyclin E and loss of p21(WAF1/CIP1) expression were significantly corr elated with decreased disease-free (P=0.037; P= 0.001) and overall(P=0.031; P=0.001) survival. Conclusions: These results suggest that immunohistochemical analysis for ce ll cycle regulators, especially cyclin E and p21(WAF1/CIP1). might be a use ful prognostic indicator in gastric cancer.